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A Tanizawa

Publications and source records attributed to A Tanizawa.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Early relapse after peripheral blood stem cell transplantation in acute myelogenous leukemia with t(8;21)].

We report a 3-year-old boy with acute myelogenous leukemia, who relapsed very early after peripheral blood stem cell transplantation (PBSCT). He was admitted with a tumor in maxillar sinus and hemorrhagic diathesis and was diagnosed as having acute myelogenous leukemia with t(8;21). He achieved complete remission with etoposide, cytosine arabinoside and mitoxantrone. After 8 courses of consolidation therapy and marrow ablative chemotherapy, he received PBSCT. G-CSF was given from day 0 because of severe infection. WBC and platelete counts rapidly increased, however, from day 20 platelet count spontaneously decreased. Concomitantly bone marrow examination revealed the presence of blastic cells. RT-PCR showed that the presence of AML 1/MTG 8 chimera mRNA in the cryopreserved PBSC samples. In vitro analysis also revealed that leukemic cells had G-CSF receptors and increased 3H-thymidine uptake in the presence of G-CSF. These findings strongly suggest that the reinfusion of leukemic cells in PBSC and the administration of G-CSF after PBSCT might be relevant to early relapse in this patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Saintopin, a dual inhibitor of DNA topoisomerases I and II, as a probe for drug-enzyme interactions.

Stabilization of the topoisomerase-cleavable complexes is the common initial event leading to the cytotoxicity of topoisomerase I and II (top1 and top2) inhibitors. Using saintopin (STP), a poison of both topoisomerases, we studied top1- and top2-cleavable complexes (Yamashita, Y., Kawada, S.-Z., Fujii, N., and Nakano, H. (1991) Biochemistry 30, 5838-5845). top1 and top2 sites induced in the presence of STP showed the same preferences for the base located 3' to the topoisomerase-induced DNA break (position +1): preference for G and not C. A camptothecin-resistant top1 with a mutation (Asn722-->Ser) next to the catalytic tyrosine (Tyr723) was cross-resistant to STP, suggesting that both STP and camptothecin interact with the protein near the catalytic tyrosine. These results are consistent with a dual interaction of the drug with the enzyme and the DNA and provide further evidence for the "drug-stacking" model. This model proposes that topoisomerase inhibitors bind, possibly through hydrogen bonding and/or stacking, with one of the bases flanking the DNA termini (guanine at position +1 in the case of STP) and within the enzyme catalytic pocket, most likely by stacking with the catalytic tyrosine.

Base Sequence↗
PubMed1994

Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials.

BACKGROUND: Camptothecins belong to a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. Two camptothecin derivatives, topotecan (TPT) and CPT-11, are in clinical trials and their chemotherapeutic efficacy appears promising. PURPOSE: Our aim was to compare simultaneously the molecular and cellular pharmacology of the various camptothecin derivatives that are presently in clinical trials. METHODS: Cytotoxicity of drugs toward human colon carcinoma HT-29 cells was determined by colony-forming assays. DNA single-strand breaks (SSB) were measured by alkaline elution. Drug potency to induce topoisomerase 1-mediated DNA cleavage and the sequence selectivity of the breaks were determined by sequencing gel autoradiography. RESULTS: SN-38 and CPT were more cytotoxic than 9-AC and TPT, and CPT-11 was almost inactive toward HT-29 cells. IC50 values were 8.8 nM for SN-38, 10 nM for CPT, 19 nM for 9-AC, 33 nM for TPT, and greater than 100 nM for CPT-11. In drug-induced DNA damage measured by alkaline elution drug concentrations producing 1000-rad-equivalents (C1000), values were 0.037 microM for SN-38, 0.051 microM for CPT, 0.085 microM for 9-AC, 0.28 microM for TPT, and greater than 1 microM for CPT-11. SN-38 remained the most potent compound in isolated nuclei, and CPT-11 was still inactive. The potency ranking was the same as in whole cells, and the C1000 values were 0.0025 microM for SN-38, 0.012 microM for CPT, 0.021 microM for 9-AC, 0.44 microM for TPT, and greater than 0.1 microM for CPT-11. Potency difference between SN-38 and the other compounds was greater in isolated nuclei than in whole cells. CONCLUSIONS: Kinetics of the reversal of drug-induced SSB in isolated nuclei suggest that dissociation of SN-38 from cleavable complexes is much slower than that of CPT. Cleavage patterns of CPT and 9-AC were similar but differed from those of TPT and SN-38. Although in vitro analyses do not necessarily reflect chemotherapeutic efficacy, this study found that SN-38 is the most potent compound and that 9-AC and TPT are less active than CPT in this system. The effect of CPT-11 is minimal. Therefore, the clinical activity of CPT-11 may strongly depend on its hydrolysis to SN-38. Differences in DNA sequence selectivity and the stability of cleavable complexes induced by the drugs may also contribute to differences among CPT derivatives.

Camptothecin↗
PubMed1994

Effects of DNA methylation on topoisomerase I and II cleavage activities.

DNA methylation is deregulated during oncogenesis. Since several major anti-cancer drugs act on topoisomerases, we investigated the effects of cytosine methylation on topoisomerase cleavage activities. Both topoisomerase I and II cleavage patterns were modified by CpG methylation in c-myc gene DNA fragments. Topoisomerase II changes, mainly cleavage reduction, occurred for methylation sites within 7 base pairs from the topoisomerase II breaks and were different for VM-26 and azatoxin. For topoisomerase I, cleavage enhancement as well as suppression were observed. Using synthetic methylated oligonucleotides, we show that hemimethylation is sufficient to alter topoisomerase I activity. Cytosine methylation on the scissile strand within the topoisomerase I consensus sequence had strong effects. Cleavage was stimulated by methylation at position -4 and was strongly inhibited by methylation at position -3 (with position -1 being the enzyme-linked nucleotide). This inhibitory effect was attributed to the presence of a methyl group in the major groove, since the transition uracil to thymine also inhibited cleavage. Altogether these results suggest an interaction of topoisomerase I with the DNA major grove at positions -3 and -4. In addition, DNA methylation may have profound effects on the activity of topoisomerases and may alter the distribution of cleavage sites produced by anticancer drugs in chromatin.

Base Sequence↗
PubMed1993

Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistance.

A camptothecin-resistant (DC3F/C-10) Chinese hamster cell line that contains a catalytically altered and camptothecin (CPT)-resistant DNA topoisomerase I (top 1) (Tanizawa, A., and Pommier, Y. (1992) Cancer Res. 52, 1848-1854) and the parent cell line (DC3F) were used to compare top 1 mRNAs and cDNAs. Northern blot analysis showed a single 4.1-kilobase band without quantitative reduction between the two cell lines. We have cloned and sequenced top 1 cDNAs. DC3F and DC3F/C-10 top 1 c-DNA are 3591 and 3626 base pair long, respectively, and encode 767 amino acids. The homology of deduced amino acid sequences between Chinese hamster and mouse or human top 1 are 98.1 and 96.7, respectively. cDNAs from DC3F/C-10 and DC3F cells differ by a single base point mutation (G to A) which results in an amino acid change from Gly505 to Ser (Gly505-->Ser). G505 corresponds to Gly503 of human top 1 cDNA and is located 220 amino acids away from the presumed catalytic Tyr725. The point mutation in the Chinese hamster top 1 is located in a region that is highly conserved among all cloned top 1 cDNAs (plant ATH, vaccinia virus, Shope fibroma virus, Drosophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, mouse, and Human). A mutation of Asp533 to Gly in this same region has been shown to confer CPT resistance for human top 1. Chinese hamster top 1 protein with a Gly505-->Ser mutation that was expressed in bacteria was resistant to CPT, indicating that this single base mutation is involved in CPT resistance. Our results suggest that the highly conserved region around Gly505 plays an important role in the interactions among top 1, DNA, and CPT.

Amino Acid Sequence↗
PubMed1993

Induction of cleavage in topoisomerase I c-DNA by topoisomerase I enzymes from calf thymus and wheat germ in the presence and absence of camptothecin.

In this study, we further examined the sequence selectivity of camptothecin in mammalian topoisomerase I cDNA from human and Chinese hamster. In the absence of camptothecin, almost all the bases at the 3'-terminus of cleavage sites are T for calf thymus and wheat germ topoisomerase I. In addition, wheat germ topoisomerase I exhibits preference for C (or not T) at -3 and for T at -2 position. As for camptothecin-stimulated cleavage with topoisomerase I, G (or not T) at +1 is an additional strong preference. This sequence selectivity of camptothecin is similar to that previously found in SV40 DNA, suggesting that camptothecin preferentially interacts with topoisomerase I-mediated cleavage sites where G is the base at the 5'-terminus. These results support the stacking model of camptothecin (Jaxel et al. (1991) J. Biol. Chem. 266, 20418-20423). Comparison of calf thymus and wheat germ topoisomerase I-mediated cleavage sites in the presence of camptothecin shows that many major cleavage sites are similar. However, the relative intensities are often different. One of the differences was attributable to a bias at position -3 where calf thymus topoisomerase I prefers G and wheat germ topoisomerase I prefers C. This difference may explain the unique patterns of cleavage sites induced by the two enzymes. Sequencing analysis of camptothecin-stimulated cleavage sites in the surrounding regions of point mutations in topoisomerase I cDNA, which were found in camptothecin-resistant cell lines, reveals no direct relationship between DNA cleavage sites in vitro and mutation sites.

Animals↗
PubMed1993

bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair.

Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclophosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand beaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks, DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.

Animals↗
PubMed1992

Topoisomerase I alteration in a camptothecin-resistant cell line derived from Chinese hamster DC3F cells in culture.

Camptothecin-resistant DC3F Chinese hamster lung fibroblast cell lines were obtained after mutagenic treatment with ethylmethanesulfonate and subsequent exposure to 1 microM camptothecin (CPT). The most resistant cell line, which was obtained after exposure to CPT for 10 days, was designated DC3F/C-10. Comparison of 50% inhibitory concentration values after 8-h CPT treatments showed that DC3F/C-10 cells were 134-fold resistant to CPT. Resistance was associated with marked reduction of CPT-induced DNA single-strand breaks and DNA-protein cross-links. This reduction was not due to reduced amounts of immunoreactive DNA topoisomerase I protein, although nuclear extracts from DC3F/C-10 cells had less enzyme catalytic activity than those from DC3F cells. Also, fast protein liquid chromatography-purified DNA topoisomerase I from DC3F/C-10 had lower specific catalytic activity than that from DC3F cells. DNA topoisomerase I from DC3F/C-10 was resistant to inhibition of catalytic activity and induction of DNA cleavage by CPT. These results suggest that CPT resistance in DC3F/C-10 cells is due to qualitative alteration of DNA topoisomerase I.

Animals↗
PubMed1992

Sling operation for male stress incontinence by utilizing modified Stamey technique.

A modified Stamey operative technique was applied to 3 men with stress incontinence due to transurethral prostatectomy or transurethral resection of bladder neck. Two pieces of polytetrafluoroethylene grafts (Gore-Tex) were positioned at the membranous and bulbous urethra as sling loops, and hung up by nylon sutures that were brought to the abdominal wall along each side of the urethra by means of a modified Stamey needle and tied over the rectus fascia. Postoperatively, maximum urethral closure pressure and functional urethral length were increased, and urinary continence was achieved in all 3 patients, however, urinary retention developed in 1 patient with bladder arefrexia.

Adult↗
PubMed1992

[Relationship between bladder trigone and bladder neck induced by traction of an indwelling balloon catheter with a spring balance and parameters of cystometrogram].

Sensation of the bladder trigone and bladder neck induced by traction of an indwelling balloon catheter with a spring balance and cystometry was evaluated in 393 males and 106 females. Male patients with an average age of 56.9 +/- 15.9 (mean +/- standard deviation) years old (range 17 to 88 years) were divided into 7 groups as follows: 19 patients without any micturitional disturbance, uregency and chronic prostatitis (11 patients), benign prostate hypertrophy (BPH) (131 patients), cervical or thoracic cord compression disorders (67 patients), lumbar vertebral disorders (114 patients), other peripheral nerve disorders associated with diabetes mellitus, post operative status of rectum cancer and others (27 patients) and brain diseases (24 patients). Female patients with an average age of 55.2 +/- 15.5 years old (range 17 to 88 years) were divided into 6 groups as follows: 24 patients without any neurological problems, urgency (7 patients), cervical or thoracic cord compression disorders (11 patients), lumbar vertebral disorders (37 patients), other peripheral nerve disorders (18 patients) and brain diseases (9 patients). The observed sensation, first desire to void (FDV) and maximum cystometric capacity (MCC) were evaluated statistically in relation to clinical factors (e.g. disease group, generation and patterns of cystometrogram). The correlation between the sensation and FDV or MCC in these patients were assessed by linear regression analysis. Sensation of normal males was 334.2 +/- 159.7 g on the average and correlated well with FDV (r = 0.88, y = 375x - 189.4). Sensation of normal females was 373.3 +/- 199.5 g on the average. However, there was no correlation (r = 0.35) between sensation and FDV in females. In males, the means of sensation obtained in patients with other peripheral nerve disorders (557.3 +/- 314.5 g) was significantly larger than the means of normal subjects (p less than 0.001), and patients with uregency and chronic prostatitis (236.4 +/- 148.3 g, p less than 0.01), BPH (424.1 +/- 215.6 g, p less than 0.001), cervical or thoracic cord compression disorders (349.0 +/- 229.5 g p less than 0.001), lumbar vertebral disorders (349.7 +/- 201.7 g, p less than 0.001) or brain diseases (490.6 +/- 305.0 g, p less than 0.05). Furthermore, the differences in the means of sensation between BPH and lumbar vertebral disorders (p less than 0.05) or brain diseases (p less than 0.05) were statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Catheterization↗
PubMed1992

[Usefulness and safety of bunazosin hydrochloride in neurogenic bladder after prolonged administration].

Bunazosin hydrochloride (Ea-0643), a selective alpha 1-blocker, was administered to 14 patients with neurogenic bladder over prolonged periods of time in order to determine its efficacy and safety. Subjective symptoms were classified into 4 grades, and their response assessed after 12 weeks of treatment. The proportion of patients showing improvement by at least one grade was 50.0% for retarded urination, 16.7% for prolonged urination, 25.0% for urinary stream condition, 25.0% for abdominal pressure at voiding, and 28.6% for residual urine. Objective symptoms were also assessed after 12 weeks of treatment, and a statistically significant improvement was recognized in the volume of spontaneously voided urine, the maximum and mean flow rates on uroflowmetry. It should be noted that both of those flow rates had improved significantly only 2 weeks into the treatment. The degree of improvement in subjective and objective symptoms and the degree of general improvement were all higher at week 12 than at week 2 of treatment. Current knowledge of the mechanism of action of this drug, coupled with the observations made in this study, suggests that, once it has improved the urodynamics, it exhibits a sustained effect for prolonged periods of treatment. However, further studies are warranted concerning the mechanisms of the pharmacological action of the drug from a pathological viewpoint. The proportion of patients in whom Ea-0643 was judged to be useful at 12 weeks of treatment was 41.7%, but when the assessment of 'slightly useful' was taken into consideration, the usefulness rate rose as high as 91.7%. Stomatitis was observed in only one case as a side effect of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

[Clinical analysis of urinary incontinence in the institutionalized elderly].

Urinary incontinence among institutionalized elderly were analyzed from clinical and social viewpoints. The patient group included 25 males and 107 females with an average age of 78 years (ranged from 66 to 92). They had neither highly impaired performance status nor severe dementia. Forty-nine of them (37%) underwent urological examination. Urge incontinence was common among male patients, while urge, stress or mixed incontinence were prevalent in female patients. Thirty-six per cent of the patients had to use pads, diapers and others for their incontinence, while other needed no special protection for their incontinence. Incontinence caused limitation of social activity in 30% of the patients. Many causal factors were assumed for incontinence in elderly; weakness of the pelvic muscles, urinary tract infection, cerebrovascular disorders, neurological disorders and prior pelvic surgery. Prostatic carcinoma or urethral stricture caused overflow incontinence in a few patients. Diuretics or tranquilizers appeared to lead incontinence in some patients. Nine of 18 patients undergoing cystometry had overactive detrusor. Majority of the incontinent elderly showed no intention to visit clinics. Therefore, it recommended to keep staffs in elderly institutions as well as elderly themselves informed that incontinence in the elderly should be treated, which in turn improves the quality of life.

Aged↗
PubMed1991

[A questionnaire survey on micturition problems among institutionalized elderly].

Prevalence of micturition problems among 1,023 institutionalized elderly was surveyed by a questionnaire. The reply was obtained from 821 elderly (80.3%) including 276 males and 545 females with ages averaged 77 years (range 61 to 96 years). They had neither highly impaired performance status nor severe dementia. Micturition problems were complained by 38% of male responders, where micturition difficulty was the most common. On the other hand, 23% of female responders answered having micturition problems and urinary frequency was the most common. One hundred and twenty-four of total responders (15%) replied to have urinary incontinence; 8% in men and 19% in women. Over half of patients with marked objective incontinence denied its presence or refused to answer. Seventy-one per cent of the incontinent elderly had no intention to receive medical care. From the above facts, it seems that many elderly have micturition problems and the incidence of urinary incontinence is latently higher than complained at survey.

Aged↗
PubMed1990

Inhibition of both etoposide-induced DNA fragmentation and activation of poly(ADP-ribose) synthesis by zinc ion.

Treatment of a human promyelocytic leukemia cell line (HL-60) with etoposide for 3-4 hrs produced an extensive degradation of DNA. Agarose gel electrophoresis showed DNA fragmentation in a nucleosomal ladder pattern. Simultaneous addition of zinc ion (ZnSO4, 1 mM) inhibited DNA fragmentation, although the amount of DNA strand breakage introduced initially by etoposide did not change significantly as measured by the DNA unwinding assay. Furthermore, zinc ion abrogated both the activation of poly(ADP-ribose) synthesis and the morphologic changes characteristic of apoptosis by etoposide. These results suggest that zinc ion inhibits a metabolic process somewhere between initial DNA cleavage through an interference with type II topoisomerase and delayed degradation of cellular DNA to a nucleosome-like pattern.

Cell Line↗
PubMed1990

Cell type dependent activation of poly (ADP-ribose) synthesis following treatment with etoposide.

Treatment of human non-lymphoid cell lines, HL-60 and U937, with etoposide stimulated poly (ADP-ribose) synthesis three- to fourfold, whereas no significant effects were observed in the lymphoid cell lines, Molt4 and CEM. This was confirmed by either an increased uptake of radio-labelled NAD into the acid-insoluble fraction or a fall in cellular NAD levels, which was counteracted by 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. On the other hand, another DNA damaging agent, N-methyl-N'-nitro-N-nitrosoguanidine augmented poly(ADP-ribose) synthesis equally in both cell types. These results taken together indicate that the activation of poly(ADP-ribose) synthesis following exposure to etoposide is a cell type specific phenomenon.

Cell Survival↗
PubMed1990

[Neurogenic bladder in patients with lumbar vertebral disorders].

Bladder and urethral functions were evaluated urodynamically in 114 patients with lumbar disorders including prolapsed lumbar intervertebral disc (66 patients), lumbar canal stenosis (19 patients), lumbar spondylolysis and/or spondylolisthesis (21 patients), lumbar spondylosis deformans (5 patients) and ossification of the yellow ligament of the lumbar spine (3 patients). The patients consisted of 88 males and 26 females with an average age of 47 years (range 17 to 73 years). Symptomatic organic infravesical obstruction was excluded by physical and radiographic examination. Cystometry revealed preoperative neurogenic bladder in 23 patients (20%); normal detrusor with overactive sphincter in 2 (9%), underactive in 8 (36%), overactive in 5 (23%) and equivocal in 7 (32%). One patient not receiving cystometry revealed abnormal uroflowmetry with 140 ml residual urine. Twenty of them underwent electromyographic examination of the external sphincter and 15 (75%) had an overactive sphincter. Nine (39%) of them complained no urological symptoms. Neurogenic bladder seemed to highly associate in those having abnormal tendon reflex in the lower extremities, decreased bulbocavernosus reflex and sensory disturbance in the perineal area, but there was no statistical significance. Of twenty-three neurogenic bladder patients, eighteen underwent a lumbar vertebral operation and fifteen received postoperative urodynamic evaluation. Uroflowmetry was improved in more than half of the patients within 3 months after the operation and cystometry was normalized in 4 of 7 patients who underwent cystometry over 6 months after the operation. Preoperative overactive detrusor remained unchanged in two of three patients who underwent cystometry over 6 months after the operation.

Adolescent↗
PubMed1990

Complete resolution of multiple pulmonary metastases of renal cell carcinoma following intravenous drip infusion of r-interleukin 2: a case report.

A 68-year-old man with multiple pulmonary metastases from a right renal cell carcinoma was treated with alpha interferon, but there was no improvement. For this reason, alpha interferon was ceased, and daily monotherapy with recombinant interleukin-2 (1,000,000 units/day) was commenced. After 4 months, plain chest x-ray and chest CT revealed complete clearance of the pulmonary metastases. There were no side effects except general fatigue and slight fever. Immunological studies revealed elevation of the leukocyte count (lymphocytes, eosinophils) and enhancement natural killer activity. At 10 months after discontinuation of the drug, recurrence has not been observed. Our case indicates the potential value of interleukin-2 following treatment with alpha interferon.

Aged↗